H2S-releasing nanoemulsions: a new formulation to inhibit tumor cells proliferation and improve tissue repair

Abstract

The improvement of solubility and/or dissolution rate of poorly soluble natural compounds is an ideal strategy to make them optimal candidates as new potential drugs. Accordingly, the allyl sulfur compounds and omega-3 fatty acids are natural hydrophobic compounds that exhibit two important combined properties: cardiovascular protection and antitumor activity. Here, we have synthesized and characterized a novel formulation of diallyl disulfide (DADS) and α-linolenic acid (ALA) as protein-nanoemulsions (BAD-NEs), using ultrasounds. BAD-NEs are stable over time at room temperature and show antioxidant and radical scavenging property. These NEs are also optimal H2S slow-release donors and show a significant anti-proliferative effect on different human cancer cell lines: MCF-7 breast cancer and HuT 78 T-cell lymphoma cells. BAD-NEs are able to regulate the ERK1/2 pathway, inducing apoptosis and cell cycle arrest at the G0/G1 phase. We have also investigated their effect on cell proliferation of human adult stem/progenitor cells. Interestingly, BAD-NEs are able to improve the Lin– Sca1+ human cardiac progenitor cells (hCPC) proliferation. This stem cell growth stimulation is combined with the expression and activation of proteins involved in tissue-repair, such as P-AKT, α-sma and connexin 43. Altogether, our results suggest that these antioxidant nanoemulsions might have potential application in selective cancer therapy and for promoting the muscle tissue repair.

Exogenous H2S exerts biphasic effects on porcine mammary epithelial cells proliferation through PI3K/Akt‐mTOR signaling pathway

“…It had been shown that H 2 S promoted the cell proliferation of human colon cancer cell (Cai, Wang, Ju, Wang, & Zhu, ), vascular endothelial cells (Papapetropoulos et al, ) and osteoblastic cell (Lv et al, ). On the contrary, H 2 S has also been reported to inhibit the cell proliferation of MCF‐7 cell (Ciocci et al, ), colon epithelial cells (Wu et al, ), and human melanoma cells (De Cicco et al, ). The complete opposite effects of H 2 S on cell proliferation might be attributed to the different cell types and culture conditions such as dose or treatment time of H 2 S. Interestingly, in our study, the results demonstrated that lower doses (< = 200 µM) of NaHS (a H 2 S donor) stimulated PMECs proliferation, while high concentration of NaHS (600 µM) inhibited PMECs proliferation.…”

“…It had been shown that H 2 S promoted the cell proliferation of human colon cancer cell (Cai, Wang, Ju, Wang, & Zhu, 2010), vascular endothelial cells (Papapetropoulos et al, 2009) and osteoblastic cell (Lv et al, 2017). On the contrary, H 2 S has also been reported to inhibit the cell proliferation of MCF-7 cell (Ciocci et al, 2016), colon epithelial cells (Wu et al, 2012) Han et al (2013) found that proliferation of lymphocytes was stimulated following treatment with NaHS at low NaHS concentrations (<1 mM) but inhibited at high NaHS concentrations (>2 mM).…”

“…In addition, H 2 S is a highly lipophilic molecule and can freely penetrate cells of all types in a receptor‐independent manner and activate various cellular targets, so as to elicit various physiological functions such as cell metabolism, cell death, and cell cycle (Mathai et al, ; Sen, ). It has been indicated that H 2 S can affect the cell proliferation of various cells, including MCF‐7 cell (Ciocci et al, ), osteoblastic cell (Lv et al, ), colon epithelial cells, (Wu et al, ) and lymphocytes (Han et al, ). However, H 2 S has quite different, even opposite effects on cell proliferation.…”

Turning regenerative technologies into treatment to repair myocardial injuries

“…Recent literature showed that synthetic microparticles coated with human stem cell membranes lead to the preservation of viable myocardium and augmentation of cardiac function in rodent models with MI . Similar microstructures loaded with natural bioactive compounds that generate a broad biological effect, such as linolenic acid, have shown a strong protective effect on cardiac cells . The cradle infrastructure can also be engraved with subsystems that release biological signals on‐demand .…”

Hydrogen Sulfide-Releasing Fibrous Membranes: Potential Patches for Stimulating the Human Stem Cells Proliferation and Viability Under Oxidative Stress.

“…The RP-HPLC analysis of the GaOS, shown in Figure 1a, indicated the presence of a main hydrophobic component (corresponding to the peaks a and b), eluted at the same retention time of DADS (see S2 Figure), which represents the major constituent (about the 60%) of the oil-garlic fraction [24]. Garlic OSCs and their conjugates have been studied as optimal H2S slow-releasing donors [23,[25][26][27]. Therefore, the ability of the GaOS solution to release H2S was here assessed by MB assay after 30 min, 2 h and 5 h of incubation at 37°C ( Figure 1B).…”